Effective control ofStaphylococcus aureuslung infection despite tertiary lymphoid structure disorganisation

Abstract

BackgroundTertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection with S. aureus but their roles remain elusive. The present study sought to examine the effects of B and/or T cell depletion on S. aureus infection and TLS development (lymphoid neogenesis) in mice.MethodsC57Bl/6 mice were pretreated with (1) an anti-CD20 mAb (B cell depletion) or (2) an anti-CD4 and/or an anti-CD8 mAbs (T cell depletion) or (3) a combination of anti-CD20, anti-CD4 and anti-CD8 mAbs (combined B and T cell depletion) or (4) with isotype control mAbs. After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containing S. aureus (106 CFU/mouse). Fourteen days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures and immunohistochemistry, respectively.ResultsFourteen days after S. aureus-bead instillation, lung bacterial load was comparable between control and lymphocyte-depleted mice. While TLS were observed in the lungs of infected mice pretreated with control mAbs, these structures were disorganised or abolished in the lungs of lymphocyte-depleted mice. The absence of CD20+ B lymphocytes had no effect on CD3+ T lymphocyte infiltration, whereas CD4+/CD8+ T-cell depletion markedly reduced CD20+ B cell infiltration. Depletion of CD4+ or CD8+ T cells separately had limited effect on B cell infiltration but lead to the absence of germinal center.ConclusionTLS disorganisation is not associated with loss of infection control in mice persistently infected with S. aureus.

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

“…Scrutiny of TLS induction in non-tumor bearing animal models has provided with crucial information for the understanding of the complex, tightly regulated, non-redundant mechanisms that lead to initiation, formation and maintenance of these lymphoid ectopic structures (55). Notably, several recent reports have shed new light in the ontogeny of TLS in mouse models of lung disorders (33,(60)(61)(62)(63)(64)(65)(66). In a model of viral infection with respiratory syncytial virus (RSV), Gassen et al reported a RSVdependent down-modulation of both IL-21 and IL-21R expression by lung Tfh cells, accompanied by an up-regulation of PD-L1 expression on resident B cells and DC, resulting in a defective GC formation and anti-RSV antibody response.…”

“…TLS are also involved in the control of lung bacterial infection ( 62 , 66 ). In Mycobacterium tuberculosis (TB) infection, they have been associated with gender bias susceptibility to TB ( 68 ).…”

Wouldn't you like to know: are tertiary lymphoid structures necessary for lung defence?

“…Second, REGARD et al [38] show that depletion of both CD4 + and CD8 + T cells markedly reduced lung TLS size and number, whereas B cell depletion did not impact T cell accumulation. This dependence on CD8 + T cells is unexpected.…”

“…In this issue of the European Respiratory Journal, REGARD et al [38] provide novel insights on a key aspect of that question, the role of TLSs in lung host defence. Those authors used their established murine model of chronic bronchial infection, which in its standard form [39,40] employs agarose beads impregnated with viable Staphylococcus aureus to induce an airway infection that persists without the need for immunosuppression or repeated challenges.…”

“…In the current study [38], the authors address that question by first using monoclonal antibodies to selectively deplete mice of B cells, CD4 + or CD8 + T cells, both types of T cells, or all three lymphocyte subsets; an isotype control group was also included. They next infected mice with S. aureus-containing beads by the intratracheal route, then examined the lungs 14 days later.…”